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Biomedical subjects

C R Smith

Publications and source records attributed to C R Smith.

At least 163 records · Page 9Linked to original sources

Recurrent encephalopathy and seizures in a US native with HTLV-I-associated myelopathy/tropical spastic paraparesis: a clinicopathologic study.

A patient with progressive spastic paraparesis originally ascribed to multiple sclerosis developed recurrent encephalopathy and seizures. A diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis was established prior to death. Autopsy confirmed chronic inflammatory myelopathy and active inflammation in the white matter of the temporal lobes.

Aged↗

Reimbursement for the oral health care of cancer patients.

Oral conditions related to cancer therapy, which are largely preventable, continue to result in considerable morbidity, dysfunction and lost quality of life. Therefore, it is important for dentists to be knowledgeable about the problems of reimbursement for the oral health care of cancer patients and become involved in the issue of access to oral health care for cancer patients.

Dental Care for Persons with Disabilities↗

The implantable defibrillator: an electronic bridge to cardiac transplantation.

BACKGROUND: Sudden cardiac death (SCD) is common among patients awaiting heart transplantation. Medical management of SCD may fail due to lack of efficacy or adverse side effects. The implantable cardioverter-defibrillator (ICD) may extend patient survival until a donor heart is available. METHODS AND RESULTS: We reviewed 16 patients listed for transplantation between November 1988 and October 1991 who underwent ICD implantation for ventricular arrhythmias refractory to medical management. Mean age was 51.4 +/- 11.4 years (range, 19-66 years), mean ejection fraction was 15.4 +/- 3.0% (range, 10-21%), and underlying cardiomyopathy was ischemic (12 patients), valvular (one patient), or dilated (three patients). There was no mortality from ICD insertion. Fourteen patients were discharged before transplantation, and two patients remained in the hospital until transplantation. Twelve patients underwent transplantation after a mean of 155.7 +/- 113.7 days (range, 3-319) on the transplant list. The ICD delivered shocks for tachyarrhythmia associated with near syncope in 15 of 16 patients. ICD shocks numbered > 10 in five patients, 5-9 in three patients, and 1-4 in seven patients. There was no morbidity or mortality attributed to patch electrode removal. CONCLUSIONS: We conclude that the ICD can be implanted with minimal morbidity in transplant candidates, allowing the patients to be ambulatory and to leave the hospital while awaiting heart transplantation. In patients at risk of SCD, the ICD is an effective electronic bridge to transplantation.

Anti-Arrhythmia Agents↗

Evaluation of surgical procedures. Changing patterns of patient selection and costs in heart transplantation.

During the past 4 years we have observed a marked increase in costs of heart transplantation in our center. This trend coincides with a shift in our recipient population toward the more severely ill patients. The percentage of patients bound for the intensive care unit has doubled. In analyzing the components of cost, we find that the length of stay, both in special care and regular nursing units, accounts for most of the cost increase. In our study of outcomes we find no significant difference in survival, at 1 month and 1 year, between recipients operated on from the intensive care unit and those not in intensive care. We find that at 1 year after transplantation, approximately 80% of patients are rehabilitated, which we define as the ability to work or to go to school. Only 20% of patients are off disability rolls, however, primarily because of problems related to insurance and the cost of continuing care, including drugs. We conclude that the comprehensive evaluation of surgical procedures requires an approach that balances costs with results on a continuing and long-term basis.

Costs and Cost Analysis↗

Management of peripheral vascular problems in recipients of cardiac allografts.

Five hundred and twenty consecutive heart transplant cases (458 adult, 62 pediatric) were reviewed to assess the impact of peripheral vascular problems. Peritransplant interventions requiring vascular cannulation (e.g., intraaortic balloon pump procedures, catheterization of the right and left sides of the heart, femoral bypass) resulted in 10 complications that necessitated nine surgical procedures. Five aortic aneurysms (three infrarenal and two suprarenal) were resected. There was one death unrelated to the aneurysm resection. Sixteen patients had evidence of peripheral vascular disease (PVD). There were three deaths in this group, none directly related to the PVD. Three patients required vascular reconstruction (axillobifemoral, bilateral femoral distal and popliteal endarterectomy) in the posttransplant period, all for advanced ischemic symptoms. Except for one patient in whom ischemia-related ulcers developed on the heels, all patients had improved or stable symptoms that did not require intervention. There were no limb losses or vascular infections. We conclude that despite the rigors of posttransplant immunosuppression, patients with stable manifestations of PVD may successfully undergo heart transplantation and subsequent vascular reconstruction, when indicated, without prohibitive risk.

Adolescent↗

Cardiac transplantation after prolonged graft preservation with the University of Wisconsin solution.

We tested the ability of University of Wisconsin solution to extend hypothermic preservation of the nonperfused heart during orthotopic baboon allotransplantation. Seven baboons received hearts after cardioplegia and storage (4 degrees C) with University of Wisconsin solution, with a preservation time of 14.2 +/- 1.6 hours. One animal died as a result of a technical error. Six survivors were immunosuppressed for 45 days and then put to death. Preservation did not alter heart weight or histologic features according to light and electron microscopy. Animals were weaned from bypass and returned to their cages without intravenous support within 3.9 +/- 0.8 hours. Weekly biopsies, electrocardiograms, enzyme analyses, echocardiograms, and right heart catheterizations demonstrated excellent cardiac function. University of Wisconsin solution can extend hypothermic cardiac preservation and has no deleterious effects on long-term myocardial function (up to 45 days). This study validates the rationale for human trials with preservation and storage in University of Wisconsin solution toward the goal of improving and prolonging donor heart preservation.

Adenosine↗

Permanent pacing following cardiac transplantation.

Permanent pacemakers were inserted in 20 of 439 patients who had received 453 orthotopic cardiac allografts since 1980 at the Columbia-Presbyterian Medical Center. Mean age at transplantation was 45 +/- 4 (SEM) years (range 10 to 64). Pacemakers were inserted an average of 2.4 +/- 1 months after transplantation (range 0.4 to 29), 16 of 20 (80%) within the first month. Indications included sinus bradycardia or sinus arrest in 15 (75%), third-degree heart block in 2 (10%), and both sinus node and atrioventricular node dysfunction in 3 (15%). Rejection episodes and pacemaker insertion were associated in 8 patients (40%). Pacing modes included DDD (7 patients, 35%), AAI,R (7 patients, 35%), VVI,R (3 patients, 15%), DDD,R (2 patients, 10%), and VVI (1 patient, 5%). There was no pacing-related morbidity or mortality. Fourteen of 20 patients (70%) are alive and well 3 to 48 months (mean 24 +/- 4) after transplantation. Late follow-up indicated that atrioventricular node dysfunction resolved in one of two patients, sinoatrial node dysfunction improved or resolved in 7/13 patients, and no atrioventricular block developed in 11 (8 to 37 months, mean 22 +/- 3). Permanent pacing can be safely performed following orthotopic cardiac transplantation, predominantly for sinus node dysfunction. The requirement for pacing may reflect ongoing or new onset rejection and patients should therefore be evaluated accordingly. Dual-chamber pacing is probably not necessary unless atrioventricular node dysfunction is coexistent. Further, as most transplant recipients return to an active life-style, AAI,R may be the preferred mode of pacing.

Adolescent↗

Septal-superior exposure of the mitral valve. The transplant approach.

The technique used for transplant recipient cardiectomy can be modified to improve exposure of the mitral valve in patients with difficult anatomy. Right atrial and septal incisions are joined at the superior end of the interatrial septum and extended across the dome of the left atrium to the base of the left atrial appendage. Retraction of the right ventricle to the left bivalves the left atrium along an axis extending from the appendage to the inferior end of the septum, producing uniquely anterosuperior exposure of the mitral apparatus. This approach provided excellent exposure in seven patients in whom there were a variety of obstacles to a conventional approach. Four (57%) had complex reoperations. There were no bleeding complications. At late follow-up there was no change in rhythm or conduction in four patients with atrial fibrillation preoperatively. A change in P wave axis and morphology was seen at late follow-up in two patients with normal sinus rhythm preoperatively, possibly related to division of the sinus node artery. A third patient with normal sinus rhythm preoperatively remained in normal sinus rhythm at late follow-up. A septal-superior approach can be useful in complex reoperations, in procedures requiring right atriotomy for other reasons, and in patients with a small or inaccessible left atrium.

Adult↗

Laser activation of tissue sealant in hand-sewn canine esophageal closure.

UNLABELLED: Dehiscence rates of esophageal anastomoses are between 5% and 20%. Because small leaks between sutures might promote microabscess formation and lead to dehiscence, we postulated that a better initial physical seal might be beneficial. Reinforcement with laser activation of tissue sealant (LATS) is a new technique that has been shown to increase the bursting strength of anastomoses in other tissues. The tissue sealant is composed of 0.4 ml of hyaluronic acid and 0.2 ml of albumin, to which 3 drops of indocyanine green dye are added to give the sealant a peak absorbance of 805 nm, matching the wavelength (808 nm) of a small, hand-held diode laser. Since tissues do not absorb at this wavelength, laser energy is focused in the sealant, minimizing collateral thermal damage. To extend this concept, we assessed LATS in a canine model of esophageal closure. The esophagus was exposed via a right thoracotomy in 20 dogs, and two transverse incisions, 2 cm in length, were made in each esophagus (n = 40 closures). Both sites were closed with a single layer of interrupted 4-0 polyglycolic acid suture. Either the proximal or distal incision was randomly chosen to receive laser activation of tissue sealant. Tissue sealant was applied to the reapproximated edges of the hand-sewn closure, which was then exposed to diode laser energy. The end point was visible shrinking and desiccation of the sealant, which required about 2 minutes. Each esophagus was recovered at 0, 2, or 7 days postoperatively (n = 10, 5, and 5 dogs, respectively), bursting pressure was measured, and the closures were examined histologically. At all three time points LATS closures had significantly higher bursting pressures than control closures (time 0: 251 +/- 87 versus 105 +/- 46, p less than 0.0001; time 2 days: 296 +/- 36 versus 121 +/- 14, p less than 0.0013; time 7 days: 318 +/- 72 versus 197 +/- 60, p less than 0.0021). Histologic study revealed trace thermal injury, with regeneration of intact mucosal lining by 7 days. CONCLUSION: laser activation of tissue sealant is a simple technique that significantly increases the strength of esophageal closure and may reduce the prevalence of dehiscence.

Adhesives↗

HA-1A. A human monoclonal antibody for the treatment of gram-negative sepsis.

HA-1A is a human monoclonal IgM antibody that binds to endotoxin. The results of the clinical trials of HA-1A demonstrate that HA-1A reduces mortality among patients with sepsis and gram-negative bacteremia. Secondary endpoints, including resolution of organ failure, discharge from intensive care unit, and discharge from the hospital, support the beneficial effects of the antibody. The antibody is well tolerated with rare side effects, including hypotension and urticarial rash. No anti-HA-1A antibodies have been detected.

Antibodies, Monoclonal↗

Infradiaphragmatic pulmonary sequestration.

The authors describe two patients with intra-abdominal pulmonary sequestration presenting as a suprarenal mass in antenatal ultrasonography (US) images. In both cases the suprarenal mass was echogenic, and in one the mass also contained small hypoechoic areas. US and computed tomography performed after birth demonstrated feeding vessels in the suprarenal mass of one neonate; colour-flow Doppler US demonstrated the smaller feeding vessels to greater advantage.

Abdominal Neoplasms↗

University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial.

We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.

Adenosine↗

University of Wisconsin solution for human donor heart preservation: initial clinical experience.

Although in vitro and primate orthotopic transplant experiments have suggested the superiority of University of Wisconsin solution (UWS) compared with crystalloid cardioplegia and saline solution storage for hypothermic heart preservation, concerns about the viscosity and the high potassium concentration of UWS have precluded its use in human cardiac transplantation. To test the safety and efficacy of UWS, 16 patients received hearts arrested with, flushed with, and stored in UWS at 4 degrees C for a mean ischemic time of 153.3 +/- 30.7 minutes. After reperfusion, the hearts contracted vigorously and attained a stable sinus rhythm within 4.0 +/- 2.4 minutes, and the patients were weaned from bypass in 24.5 +/- 8.0 minutes. There was no evidence of acute or chronic ischemic myocardial injury by enzymatic analysis, electrocardiography, or biopsy specimen histology. The results suggest UWS can be safely used, within currently accepted limits of donor ischemic time, to arrest and preserve human hearts for transplantation. Further studies of preservation are required to compare UWS with crystalloid cardioplegia and saline solution storage and to test the ability of UWS to prolong the period of safe donor hypothermic ischemia in clinical heart transplantation.

Adenosine↗

Motility of bile canaliculi in the living animal: implications for bile flow.

Modern fluorescence microscopic techniques were used to image the bile canalicular system in the intact rat liver, in vivo. By combining the use of sodium fluorescein secretion into bile, with digitally enhanced fluorescence microscopy and time-lapse video, it was possible to capture and record the canalicular motility events that accompany the secretion of bile in life. Active bile canalicular contractions were found predominantly in zone 1 (periportal) hepatocytes of the liver. The contractile movements were repetitive, forceful, and appeared unidirectional moving bile in a direction towards the portal bile ducts. Contractions were not seen in the network of canaliculi on the surface of the liver. Cytochalasin B administration resulted in reduced canalicular motility, progressive dilation of zone 1 canaliculi, and impairment of bile flow. Canalicular dilations invariably involved the branch points of the canalicular network. The findings add substantively to previous in vitro studies using couplets, and suggest that canalicular contractions contribute physiologically to bile flow in the liver.

Animals↗

Deep hypothermic circulatory arrest for the management of complex anterior and posterior circulation aneurysms.

Giant aneurysm surgery continues to be a technically difficult task with high operative morbidity. Recent advances in cardiac surgery have fueled interest in the technique of deep hypothermic circulatory arrest for the treatment of giant and complex intracranial aneurysms. Fourteen patients with giant intracranial aneurysms operated on with the technique of deep hypothermic circulatory arrest are presented. All 14 aneurysms were successfully treated. There were 2 intraoperative strokes: 1 resulted in severe disability and 1 resulted in mild disability. No significant neurological complications were related to the technique of cardiopulmonary bypass with deep hypothermic circulatory arrest. This initial experience indicates that patients with giant and complex intracranial aneurysms might benefit from a surgical approach that included the use of deep hypothermic circulatory arrest.

Adolescent↗

Beta-adrenergic receptor sensitivity and guanine nucleotide regulatory proteins in transplanted human hearts and autotransplanted baboons.

This study was conducted in human subjects and in baboons to assess elements of the beta-adrenergic receptor complex in vivo and in vitro following cardiac transplantation. In human subjects, the concentration at which administered isoproterenol increased heart rate by 25 beats per min was within the normal range (mean, 3.2 +/- 0.4 micrograms). Myocardial biopsies and lymphocytes were obtained from 14 transplant recipients undergoing routine right heart catheterization. The stimulatory guanine nucleotide regulatory protein, Gs, was significantly greater in the lymphocyte than in right ventricular myocardium (5.8 +/- 1.7 vs. 2.0 +/- 0.5 relative to standard rat heart membrane preparation, P less than 0.05). In contrast, Gi was significantly greater in the myocardium than in the lymphocyte (4.2 +/- 1.3 vs. 1.1 +/- 0.3, P less than 0.025). There was no correlation between lymphocyte and cardiac G protein determinations. In the autotransplanted baboon heart, beta-receptors were increased (73 +/- 4 vs. 36 +/- 10 fmol/mg, P less than 0.05). Gs was not significantly different in denervated myocardial tissue vs. control cardiac tissue (1.1 +/- 0.2 vs. 0.8 +/- 0.2, P greater than 0.05). However, the inhibitory G protein, Gi, was significantly greater in transplanted animals (0.4 +/- 0.1 vs. 0.2 +/- 0.04, P less than 0.05). Relative enrichment of a Gi-like protein in the autotransplanted baboon heart was associated with a non-statistically significant trend towards a uniform reduction in basal and Gs-mediated adrenergic effects on adenylate cyclase activity. Despite the lack of biochemical evidence of enhanced beta-adrenergic receptor-mediated adenylate cyclase coupling, denervation in the autotransplanted baboon was associated with in vitro evidence of chronotropic and inotropic supersensitivity to isoproterenol. The results call into question the notion of adrenergic hypersensitivity in human subjects following cardiac transplantation, indicate the potential role for guanine nucleotide regulatory proteins in mediating responses of the denervated heart, and distinguish between several characteristics of the chronically denervated, transplanted human heart compared with the acutely auto-denervated of the baboon heart.

Adenylyl Cyclases↗

Effect of massive intraoperative thiopental loading on cardiovascular hemodynamics and myocardial performance.

Anesthetics that protect the brain may also depress the heart. We recently anesthetized a patient with a giant cerebral aneurysm of the basilar artery who had it clipped during circulatory arrest. Thiopental loading was carried out prior to and during cardiopulmonary bypass, and we monitored transesophageal echocardiographic function and the hemodynamic profile throughout. The patient demonstrated little change in cardiovascular parameters or myocardial performance, and we conclude that the massive dose of thiopental was well tolerated.

Journal Article↗